The Hox genes encode a conserved family of homeodomain-containing transcriptional regulators that are critical for many aspects of animal development, in all metazoans. The long-term goal of this project is to understand how these proteins function as transcriptional regulators at a mechanistic level. Three approaches will be used: 1) a structure-function analysis of three Hox proteins, using an in vivo, rescue-based strategy, focusing especially on Hox protein motifs that interact with Hox cofactors in a context-dependent manner, 2) the high-resolution characterization of individual Hox- targeted regulatory elements, and 3) an analysis of the Hox-dependent chromatin architectures in the imaginal discs, the precursors of the adult fly. Together, these studies will provide important insights int how these and other transcriptional regulators carry out their specific functions during animal development. PUBLIC HEALTH RELEVANCE: This project will investigate the mechanism by which the Hox family of transcriptional regulators controls their downstream target genes in Drosophila. Emphasis is placed on using rescuing transgenes to carry out a structure-function analysis of conserved protein motifs as well as on mechanistic studies of individual, Hox-regulated elements. An analysis of Hox-dependent tissue-specific chromatin structures will also be executed.